The xenotropic (X-tropic) C-type virus was originally detected in New Zealand Black (NZB) mice, a strain with an inherited syndrome of autoimmunity and cancer. X-tropic viruses cannot exogenously infect mouse cells but productively infect cells from many heterologous species including birds. All cells from NZB mice spontaneously release large quantities of the virus, whereas cells from other mouse strains produce the virus at less frequency and titer. Individual cells from NZB mice also differ in extent of virus production. These intracellular as well as extracellular controls of X-tropic viruses are being studied. Various virus isolates are being characterized to determine if different subclasses of X-tropic viruses exist. The presence of infectious virus in embryos and developing eggs is being studied and the effect of virus infection on embryonic development and the sensitivity of developing eggs to C-type virus infection is also being examined. We are evaluating, as well, the expression of X-tropic virus in the pancreas during differentiation and are continuing experiments examining the possible role of the virus in the immune-complex nephritis of NZB/W mice. Phenotypically mixed murine and avian C-type viruses are being used to examine further the mechanism and control of type C virus assembly, replication and transformation. We shall study the role of the serum factor associated with mouse lipoproteins which neutralizes specifically X-tropic virus. By interacting with virus antigen on the cell surface, this factor may regulate X-tropic virus expression and influence normal development. These studies are aimed at uncovering the role the X-tropic viruses may play in maturation and in aging processes such as autoimmunity and cancer.